LINC00665 promotes the viability, migration and invasion of T cell acute lymphoblastic leukemia cells by targeting miR-101 via modulating PI3K/Akt pathway
LINC00665 promotes the viability, migration and invasion of T cell acute lymphoblastic leukemia cells by targeting miR-101 via modulating PI3K/Akt pathway
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DOI：
10.1016/j.tice.2021.101579
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发表时间：
2021-06-23
期刊：
影响因子：
2.6
通讯作者：
Gu, A. Er Zi
中科院分区：
文献类型：
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作者：
Abuduer, Muhebaier;Gu, A. Er Zi
T细胞急性淋巴细胞白血病（T-ALL）是一种高危恶性肿瘤。癌症生长相关的长基因间非蛋白编码RNA 665 (LINC00665)在T-ALL中的作用仍不清楚，因此本研究对此进行了进一步的探索。使用基因表达谱交互分析 (GEPIA) 2 分析急性髓系白血病 (LAML) 组织和髓系组织中 LINC00665 的表达。通过 LncBase Predicted v.2 预测 LINC00665 的靶标 microRNA (miR)，并使用双荧光素酶报告基因测定进行验证。 T-ALL细胞中LINC00665和miR-101过表达或沉默后，使用细胞计数试剂盒8和Transwell实验检测细胞的活力、迁移和侵袭。采用实时定量聚合酶链反应（qRT-PCR）和蛋白质印迹法检测LINC00665、miR-101、Cyclin D1、基质金属蛋白酶（MMP）-2、MMP-9、磷酸化（p）-磷脂酰肌醇3-激酶（PI3K）、PI3K、p-Akt、Akt的表达。 LINC00665在LAML组织、T-ALL患者的外周血样本和T-ALL细胞中呈高表达。 LINC00665的过表达促进了T-ALL细胞的活力、迁移和侵袭，并下调了miR-101的表达，而LINC00665的沉默则相反。 MiR-101可以竞争性地结合LINC00665，并且在T-ALL中低表达。 MiR-101 模拟物抑制 T-ALL 细胞的活力、迁移和侵袭，并逆转过表达的 LINC00665 的影响，而 miR-101 抑制剂则逆转 LINC00665 沉默的影响。此外，过表达的LINC00665上调了Cyclin D1 MMP-2和MMP-9的表达以及p-PI3K/PI3K和p-Akt/Akt的比率，而miR-101模拟物可逆转这一现象。 LINC00665 可通过激活 PI3K/Akt 通路靶向 miR-101，从而增强 T-ALL 细胞的活力、迁移和侵袭能力。
T cell acute lymphoblastic leukemia (T-ALL) is a high-risk malignancy. The effects of cancer growth-related Long Intergenic Non-Protein Coding RNA 665 (LINC00665) in T-ALL remained obscure, and therefore further exploration was conducted on that in this study. The expression of LINC00665 in acute myeloid leukemia (LAML) tissues and myeloid tissues was analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) 2. The target microRNA (miR) of LINC00665 was predicted by LncBase Predicted v.2 and verified using dual-luciferase reporter assay. After LINC00665 and miR-101 in T-ALL cells were overexpressed or silenced, the viability, migration and invasion of cell were detected using cell counting kit-8 and Transwell assays. The expressions of LINC00665, miR-101, Cyclin D1, Matrix metalloproteinases (MMP)-2, MMP-9, phosphorylated (p)-phosphatidylinositol 3-kinase (PI3K), PI3K, p-Akt, Akt were detected by quantitative real-time Polymerase Chain Reaction (qRT-PCR) and western blot. High expression of LINC00665 was presented in LAML tissues, the peripheral blood samples from patients with T-ALL and T-ALL cells. Overexpression of LINC00665 promoted the viability, migration and invasion of T-ALL cells and downregulated miR-101 expression, whereas silencing of LINC00665 did oppositely. MiR-101 could competitively bind to LINC00665, and was low-expressed in T-ALL. MiR-101 mimic inhibited viability, migration and invasion of T-ALL cells, and reversed effects of overexpressed LINC00665, whilst miR-101 inhibitor reversed the effects of LINC00665 silencing. Besides, overexpressed LINC00665 upregulated the expressions of Cyclin D1 MMP-2, and MMP-9 and the ratios of p-PI3K/PI3K and p-Akt/Akt, which were reversed by miR-101 mimic. LINC00665 could enhance the viability, migration and invasion abilities of T-ALL cells by targeting miR-101 via activating PI3K/Akt pathway.